Dissolvable Core-Shell Microneedle Patch for Biphasic Drug Delivery To Enhance Diabetic Wound Healing.

Diabetic wounds constitute one of the most prevalent complications among diabetic patients, characterized by a low healing rate and a high recurrence rate. These wounds frequently result in ulceration, amputation, and, in severe cases, life-threatening conditions. The difficulty of wound healing in diabetic patients is primarily attributed to the invasion of pathogenic bacteria, dysregulation of the inflammatory response, and insufficient angiogenesis. In this study, we developed a core-shell microneedle (MN) patch that delivers antimicrobial agents, anti-inflammatory agents, and angiogenic agents in a biphasic release mode for the treatment of diabetic wound healing. Tetracycline hydrochloride (TCH) and drug-carrying nanoparticles (SIM-PLGA NPs) were coated in the inner layer of the tip to respond to early bacterial infection and subsequently induce angiogenesis. Metformin hydrochloride (Met) was loaded onto the outer shell of the needle tip to regulate the inflammatory response. The core-shell MN patch (TCH/SIM-PLGA NPs/Met MN) inhibited bacterial infection and promoted cell migration and angiogenesis. The application of the TCH/SIM-PLGA NPs/Met MN patch in the constructed diabetic wound model reduced inflammation, induced angiogenesis, encouraged collagen deposition and tissue regeneration during wound healing and repair, and accelerated diabetic wound closure. This biphasic release system, combined with MN, exhibits significant potential for broader applications in wound healing.